Inhaled nitric oxide (INO) is an exciting new therapy being used in newborns with severe lung disease which has shown great success in large clinical studies. Nitric oxide (NO) was a molecule previously known only as an environmental pollutant found in car exhaust and cigarette smoke. However, NO has been found to dilate the blood vessels in the lung enabling injured lungs to transfer oxygen and carbon dioxide more effectively. The long term effects of its use in newborn infants are not known. The project proposes to investigate whether INO therapy causes evidence of injury similar to that which is seen with prolonged exposure to oxygen. Evidence of this type of injury will be sought by doing laboratory studies on the blood of infants receiving NO and oxygen and oxygen alone. These results will also be compared to samples from normal infants. The samples are drawn from infants in the Intensive Care Nursery at Packard Children's Hospital and the studies are processed in Dr. Phyllis Dennery's laboratory. Preliminary results demonstrate a definite increase in oxidative injury and depleted antioxidant defenses in infants receiving NO when compared to infants receiving high oxygen concentrations. While NO appears to be an important therapy for severe respiratory failure, prolonged use may be associated with adverse consequences such as chronic lung disease. This project has the ability to benefit children by increasing the knowledge about the toxicities of INO therapy. If signficant abnormalities are found with INO therapy, this information will be critical to guide further use of this therapy in newborns.